Comparing lesion segmentation methods in multiple sclerosis: Input from one manually delineated subject is sufficient for accurate lesion segmentation.

PURPOSE: Accurate lesion segmentation is important for measurements of lesion load and atrophy in subjects with multiple sclerosis (MS). International MS lesion challenges show a preference of convolutional neural networks (CNN) strategies, such as nicMSlesions. However, since the software is trained on fairly homogenous training data, we aimed to test the performance of nicMSlesions in an independent dataset with manual and other automatic lesion segmentations to determine whether this method is suitable for larger, multi-center studies. METHODS: Manual lesion segmentation was performed in fourteen subjects with MS on sagittal 3D FLAIR images from a 3T GE whole-body scanner with 8-channel head coil. We compared five different categories of automated lesion segmentation methods for their volumetric and spatial agreement with manual segmentation: (i) unsupervised, untrained (LesionTOADS); (ii) supervised, untrained (LST-LPA and nicMSlesions with default settings); (iii) supervised, untrained with threshold adjustment (LST-LPA optimized for current data); (iv) supervised, trained with leave-one-out cross-validation on fourteen subjects with MS (nicMSlesions and BIANCA); and (v) supervised, trained on a single subject with MS (nicMSlesions). Volumetric accuracy was determined by the intra-class correlation coefficient (ICC) and spatial accuracy by Dice's similarity index (SI). Volumes and SI were compared between methods using repeated measures ANOVA or Friedman tests with post-hoc pairwise comparison. RESULTS: The best volumetric and spatial agreement with manual was obtained with the supervised and trained methods nicMSlesions and BIANCA (ICC absolute agreement > 0.968 and median SI > 0.643) and the worst with the unsupervised, untrained method LesionTOADS (ICC absolute agreement = 0.140 and median SI = 0.444). Agreement with manual in the single-subject network training of nicMSlesions was poor for input with low lesion volumes (i.e. two subjects with lesion volumes ≤ 3.0 ml). For the other twelve subjects, ICC varied from 0.593 to 0.973 and median SI varied from 0.535 to 0.606. In all cases, the single-subject trained nicMSlesions segmentations outperformed LesionTOADS, and in almost all cases it also outperformed LST-LPA. CONCLUSION: Input from only one subject to re-train the deep learning CNN nicMSlesions is sufficient for adequate lesion segmentation, with on average higher volumetric and spatial agreement with manual than obtained with the untrained methods LesionTOADS and LST-LPA.

Excited state intramolecular proton transfer in hydroxyanthraquinones: Toward predicting fading of organic red colorants in art.

Compositionally similar organic red colorants in the anthraquinone family, whose photodegradation can cause irreversible color and stability changes, have long been used in works of art. Different organic reds, and their multiple chromophores, suffer degradation disparately. Understanding the details of these molecules' degradation therefore provides a window into their behavior in works of art and may assist the development of improved conservation methods. According to one proposed model of photodegradation dynamics, intramolecular proton transfer provides a kinetically favored decay pathway in some photoexcited chromophores, preventing degradation-promoting electron transfer (ET). To further test this model, we measured excited state lifetimes of substituted gas-phase anthraquinones using high-level theory to explain the experimental results. The data show a general structural trend: Anthraquinones with 1,4-OH substitution are long-lived and prone to damaging ET, while excited state intramolecular proton transfers promote efficient quenching for hydroxyanthraquinones that lack this motif.

Characterizing the dark state in thymine and uracil by double resonant spectroscopy and quantum computation.

We report on gas phase double resonant spectroscopy of both the ground state and the dark excited state in isolated uracil and thymine. We also report lifetimes of the dark state for different excitation wavelengths. In combination with ab initio calculations the results suggest that the dark state is of triplet ((3)ππ*) character.

Pairing of isolated nucleic-acid bases in the absence of the DNA backbone.

The two intertwined strands of DNA are held together through base pairing--the formation of hydrogen bonds between bases located opposite each other on the two strands. DNA replication and transcription involve the breaking and re-forming of these hydrogen bonds, but it is difficult to probe these processes directly. For example, conventional DNA spectroscopy is dominated by solvent interactions, crystal modes and collective modes of the DNA backbone; gas-phase studies, in contrast, can in principle measure interactions between individual molecules in the absence of external effects, but require the vaporization of the interacting species without thermal degradation. Here we report the generation of gas-phase complexes comprising paired bases, and the spectroscopic characterization of the hydrogen bonding in isolated guanine-cytosine (G-C) and guanine-guanine (G-G) base pairs. We find that the gas-phase G-C base pair adopts a single configuration, which may be Watson-Crick, whereas G-G exists in two different configurations, and we see evidence for proton transfer in the G-C pair, an important step in radiation-induced DNA damage pathways. Interactions between different bases and between bases and water molecules can also be characterized by our approach, providing stringent tests for high-level ab initio computations that aim to elucidate the fundamental aspects of nucleotide interactions.

Comparative mass spectrometric analyses of Photofrin oligomers by fast atom bombardment mass spectrometry, UV and IR matrix-assisted laser desorption/ionization mass spectrometry, electrospray ionization mass spectrometry and laser desorption/jet-cooling photoionization mass spectrometry.

Photofrin (porfimer sodium) is a porphyrin derivative used in the treatment of a variety of cancers by photodynamic therapy. This oligomer complex and a variety of porphyrin monomers, dimers and trimers were analyzed with five different mass spectral ionization techniques: fast atom bombardment, UV and IR matrix-assisted laser desorption/ionization, electrospray ionization, and laser desorption/jet-cooling photoionization. All five approaches resulted in very similar oligomer distributions with an average oligomer length of 2.7 +/- 0.1 porphyrin units. In addition to the Photofrin analysis, this study provides a side-by-side comparison of the spectra for the five different mass spectrometric techniques.

Fragment-Free Mass Spectrometric Analysis with Jet Cooling/VUV Photoionization.

We show that it is possible to obtain fragment-free mass spectra of large molecules by a combination of laser desorption, jet cooling, and VUV single-photon photoionization. The ability to obtain parent molecular masses is particularly important for the analysis of mixtures, such as combinations of fully saturated hydrocarbons. By varying the cooling conditions, we can also achieve partial fragmentation in order to obtain further structural information. The use of different wavelengths provides additional selectivity between aromatic and aliphatic compounds.

A search for C60 in carbonaceous chondrites.

Analysis of interior samples of the Murchison meteorite by two routes yielded an upper limit of 2 ppb for its C60 content, as compared to parts per million levels for individual polycyclic aromatic hydrocarbons (PAHs). Provided the samples contain an interstellar component, which is probable since Murchison hydrocarbons contain excess deuterium, this result argues against the ubiquitous presence of C60 in the interstellar medium. A possible explanation for the absence of C60 was found in experiments showing how PAHs replace fullerenes as stable end products when hydrogen is present during carbon condensation. As a secondary result we found high molecular weight PAHs in the Murchison and Allende meteorites. Coronene and its methyl derivatives are especially interesting since features in the coronene spectrum have been shown to match some of the unidentified interstellar infrared emission bands.

Scandium clusters in fullerene cages.

The production and spectroscopic characterization of fullerene-encapsulated metal-atom clusters is reported. In particular, both solution and solid-state electron paramagnetic resonance (EPR) spectra of Sc(3)C(82) have been obtained. ScC(82) also gives an EPR spectrum, but Sc2Cn species-the most abundant metallofullerenes in the mass spectrum-are EPR-silent even though Sc(2) is EPR-active in a rare-gas matrix at 4.2 K. The results suggest that the three scandium atoms in Sc(3)C(82) form an equilateral triangle-as was previously suggested for Sc(3) molecules isolated in a cryogenic rare-gas matrix. The spectrum of ScC(82) has features similar to those found earlier for LaC(82) and YC(82), suggesting that it can also be described as a +3 metal cation within a -3 fullerene radical anion. An implication of this work is that production of macroscopic quantities of clustercontaining fullerenes may make possible the fabrication of exotic new structures with regular arrays of metal-atom clusters isolated in fullerene molecules, resulting in a new type of host/guest nanostructured material.